New tuberculosis therapy offers potential shorter treatment

Phase III Trials Planned in Africa

16 December 2005 | Washington, D.C. -Clinical results on a new combination treatment that could dramatically shorten the length of tuberculosis (TB) treatment were presented today at the 45 th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, D.C.

The phase II trial results of a gatifloxacin-containing regimen are demonstrating good potential. The regimen is significantly more potent than the currently recommended six-month regimen of isoniazid, rifampicin, pyrazinamide and ethambutol, and suggests that when gatifloxacin is used instead of ethambutol, the standard six-month regimen may be shortened to four months. "We are working to bring together public and private partners to speed development for this new treatment," says Dr. Robert Ridley, Director of the World Health Organization-based Special Programme for Research and Training in Tropical Diseases (TDR). This is the most advanced shorter TB treatment regimen presently in development, and could be available to the public by the end of 2009 if positive results continue.

Finding options to shorten the length of treatment has been declared a public health priority by the Stop TB partnership. "The gatifloxacin fixed-dose combination responds to the new WHO Stop TB Strategy's call for new tools, in particular, new regimens that can significantly shorten the current six-month treatment time," said Dr. Mario Raviglione, Director of WHO's Stop TB.

One-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of TB, with approximately eight million people developing the active form of the disease every year. The HIV/AIDS pandemic has dramatically increased the incidence of this disease. A shorter TB regime will also help improve treatment adherence and preventing the development of multidrug-resistant TB.

The phase II trial was conducted by the South African Medical Research Council in Durban, South Africa, in patients with newly diagnosed pulmonary tuberculosis with and without HIV co-infection. It was designed to measure the anti-tuberculosis activity of the treatment in the first two months of therapy when compared to standard WHO recommended treatment and two other similar regimens which contained either ofloxacin or moxifloxacin. Treatment with either the gatifloxacin or moxifloxacin containing regimen was shown to be significantly more active than either the standard regimen or the ofloxacin containing regimen after two months of treatment. A multi-centre Phase III clinical trial is planned to definitely assess whether the four month gatifloxacin containing regimen is equivalent to the current standard six month short course regimen. Study sites are in Benin, Guinea, Kenya, Senegal and South Africa. Arnd Hoeveler, of the European Commission (EC), says, "The clinical trial sites are the result of an EC funded Consortium of ten European and African institutions (the OFLOTUB Consortium) that are in the process of finalizing the terms of a proposed collaboration with the WHO to develop a new short course treatment regimen. We are delighted to contribute to this effort."

The research is planned to continue as part of an international collaboration which is being developed between the World Health Organization-based Special Programme for Research and Training in Tropical Diseases (TDR), the European Commission (EU), the OFLOTUB Consortium that is coordinated by the French Institut de Recherche pour le Dévelopement (IRD), and Lupin Pharmaceuticals, Ltd. “The IRD is extremely proud to have significantly contributed to the foundation of this collaborative effort,” says Jean François Girard, chairman of IRD.

About WHO/TDR

The Special Programme for Research and Training in Tropical Diseases (TDR) is a global programme of scientific collaboration established in 1975, sponsored by the World Health Organization, World Bank, United Nations Development Programme and United Nations Children's Fund, and based in Geneva, Switzerland. Its focus is research into neglected diseases of the poor, with the goal of improving existing approaches and developing new ways to prevent, diagnose, treat and control these diseases.

About the OFLOTUB Consortium

OFLOTUB is a consortium of ten partners from Europe and Africa that was initiated in 2002 to undertake Phase II and Phase III trials to test the safety and efficacy of a gatifloxacin-containing 4-month treatment regimen for the treatment of TB. It was established under the auspices of the European Commission and is coordinated by the Institut de Recherche pour le Dévelopement (IRD) in Paris, France. Through the conduct of the Phase II and III trials, the objective of the Consortium is to contribute to the development of research capacities and the reinforcement of structures to conduct clinical trials respecting international standards of care in Africa.

About IRD

Originally founded in 1944, the Institut de recherche pour le développement is a public science and technology research institute, reporting to the French ministries in charge of research and development cooperation. IRD researches focus on the relationship between man and the environment in the tropical and mediterranean countries, with a view to contributing to the sustainable development of those countries. The aims of IRD activities are to respond to the major development challenges facing Southern countries: societies and health, earth and environment, and living resources.